Extracellular zinc and ATP-gated P2X receptor calcium entry channels: New zinc receptors as physiological sensors and therapeutic targets.

Purinergic Signalling
Erik M SchwiebertAkos Zsembery

Abstract

In this review, we focus on two attributes of P2X receptor channel function, one essential and one novel. First, we propose that P2X receptors are extracellular sensors as well as receptors and ion channels. In particular, the large extracellular domain (that comprises 70% of the molecular mass of the receptor channel protein) lends itself to be a cellular sensor. Moreover, its exquisite sensitivity to extracellular pH, ionic strength, and multiple ligands evokes the function of a sensor. Second, we propose that P2X receptors are extracellular zinc receptors as well as receptors for nucleotides. We provide novel data in multiple publications and illustrative data in this invited review to suggest that zinc triggers ATP-independent activation of P2X receptor channel function. In this light, P2X receptors are the cellular site of integration between autocrine and paracrine zinc signaling and autocrine and paracrine purinergic signaling. P2X receptors may sense changes in these ligands as well as in extracellular pH and ionic strength and transduce these sensations via calcium and/or sodium entry and changes in membrane potential.

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Citations

Mar 28, 2008·Purinergic Signalling·Erik M Schwiebert, J Gregory Fitz
Apr 29, 2008·Purinergic Signalling·Michael B HovaterErik M Schwiebert
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Dec 4, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Cara L SherwoodScott Boitano
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Dec 15, 2010·Cell Calcium·Gergely KovacsMatthias A Hediger
Jul 1, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·F Sáez-OrellanaJ Fuentealba
Jan 19, 2021·Neuroscience·Rebecca F KrallElias Aizenman

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Methods Mentioned

BETA
glycosylation
fluorescence imaging

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